Stem Cells: Viable Option for CHF or Pipe Dream?

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A Cochrane systematic review and meta-analysis of bone-marrow-derived stem cells (BMSCs) in patients with ischemic heart disease or congestive heart failure, found slight evidence to suggest a benefit for stem-cell therapy in those populations.

Point out that even though BMSC treatment appears to be safe and effective, the review was limited by the small size of the included studies, the low numbers of events, possible publication bias, and the large number of comparisons performed, which might have led to false-positive results.

By pooling all available results from trials of bone-marrow-derived stem cells (BMSCs) in patients with ischemic heart disease or congestive heart failure, a Cochrane review found slight evidence to suggest a benefit for stem-cell therapy in those populations.

"At present, these results provide some evidence that stem-cell treatment may be of benefit in people both with chronic ischemic heart disease and with heart failure. Adverse events are rare, with no long-term adverse events reported," the authors wrote.

"However, the quality of the evidence is relatively low because there were few deaths and hospital readmissions in the studies, and individual study results varied," they added. "Although BMSC treatment has the potential to be used in clinical practice for people with heart failure and for those with no other treatment option, the results of this review warrant larger clinical trials to confirm the present findings."

Clyde Yancy, MD, of the Northwestern University Feinberg School of Medicine, expressed disappointment about the results because of the low numbers of patients included in the reviewed trials, which spanned several years.

"I know these studies are difficult -- and I've been directly involved in several -- but at a certain point in time we have to call the question and say, 'Do we know anything more now, are we any closer to the clinical application of these technologies than we were a decade ago?'" he told MedPage Today. "The answer in a very disappointing way is 'No.'"

"It doesn't mean we shouldn't continue the pursuit, but it at least points out how difficult it is, and it points out ... how unrewarding it has been up until this time," he said, adding that he remains hopeful that regenerative therapies will gain a clinical application in his lifetime.

To review the overall body of evidence, Martin-Rendon and colleagues collected data from randomized trials conducted through March 2013 that compared the use of autologous adult stem/progenitor cells with no cells/placebo. They identified 23 trials with a total of 1,137 participants diagnosed with ischemic heart disease or congestive heart failure, after excluding those with acute MI.

The average age of the patients ranged from 53 to 70, and the duration of follow-up ranged from 3 months to 5 years.

During follow-up lasting less than a year, there were no significant differences between the BMSC and control groups in mortality (RR 0.68, 95% CI 0.32-1.41) or rehospitalization for heart failure (RR 0.36, 95% CI 0.12-1.06), although an advantage for BMSC therapy did emerge over the longer term.

According to moderate-quality evidence, BMSC therapy also improved various other endpoints relative to control:

Left ventricular end-systolic volume (mean improvement 5.47 mL in the short term and 14.64 mL in the long term)

Stroke volume index (mean difference 3.84 in the short term and 6.52 in the long term)

Left ventricular ejection fraction (mean difference 4.22% in the short term and 2.62% in the long term)

New York Heart Association class (mean improvement 0.63 in the short term and 0.91 in the long term)

Canadian Cardiovascular Society score (mean improvement 0.81 in the short term)

Subgroup analyses showed that the way the stem cells were administered, baseline ejection fraction, cell type, and the clinical status of the patients -- but not cell dose -- all influenced the observed effects, according to the authors.

Only 19 of the trials reported adverse events, and in those, only four patients had one -- one hematoma related to bone marrow harvest and three cases of pulmonary edema during injection of the cells.

But even though BMSC treatment appears to be safe and effective, the review was limited by the small size of the included studies, the low numbers of events, possible publication bias, and the large number of comparisons performed, which might have led to false-positive results.

"There is a clear need for large-scale, adequately powered studies with well-defined participant cohorts and long-term follow-up to confirm the beneficial effects of BMSC in terms of reduced mortality and rehospitalization, and improved cardiac function," the authors wrote.

They acknowledged, however, that "the potential for a large, funded clinical trial is limited, as there are no intellectual property rights associated with this procedure in its current form, rendering it unattractive to private company funding."

The review received internal support from NHS Blood and Transplant, Research and Development, and the William Harvey Research Institute, and external support from the National Institute for Health Research and the Oxford Biomedical Research Center Program -- all in the U.K.

Martin-Rendon disclosed working at the Stem Cell Research Laboratory, NHS Blood and Transplant, at John Radcliffe Hospital in Oxford, England. One of the other authors disclosed being the lead investigator of the ongoing BAMI trial, which is a European phase III trial to test the clinical efficacy of stem-cell therapy for acute myocardial infarction.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner